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P53 Signaling

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p53 is a tumour suppressor protein that regulates the expression of a wide variety of genes involved in Apoptosis, Growth arrest, Inhibition of cell cycle progression, Differentiation and accelerated DNA repair or Senescence in response to Genotoxic or Cellular Stress. As a transcription factor, p53 is composed of an N-terminal Activation Domain, a central specific DNA Binding Domain, and a C-terminal Tetramerization Domain, followed by a Regulatory Domain rich in basic Amino acids. Having a short half-life, p53 is normally maintained at low levels in unstressed mammalian cells by continuous ubiquitylation and subsequent degradation by the 26S Proteasome. Nonphosphorylated p53 is ubiquitylated by the MDM2 (Mouse Double Minute-2) ubiquitin ligase. MDM2 binding inactivates p53 by two mechanisms. First, MDM2 binds [...]


1.Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome.
Mirzayans R, Andrais B, Kumar P, Murray D.
Int J Mol Sci. 2017 Apr 28;18(5). pii: E928. doi: 10.3390/ijms18050928. Review.
2.The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.
Sparks A, Dayal S, Das J, Robertson P, Menendez S, Saville MK.
Oncogene. 2014 Sep 18;33(38):4685-96. doi: 10.1038/onc.2013.413. Epub 2013 Oct 14.
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